Population Pharmacokinetics and Dosing Simulations of Ceftazidime in Chinese Neonates

Wang, Honghong; Li, Xingang; Sun, Shusen; Mao, Guifu; Ping, Xiao; Chan, Frank; Liang, Zhuoxin; Min, Zheng; Huang, Yingna; Tang, Haitao; Ou, Renhao; Ni, Yang; Ling, Xi; Zhi-gang, Zhao

doi:10.1016/j.xphs.2017.12.018

Cited by 12 publications

(12 citation statements)

References 21 publications

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“…The Phoenix NLME software (Certara, Inc.) was used to conduct simulations to achieve an optimal individualised dosing regimen for different patient subgroups, and we subsequently developed a simple and practical dosage regimen table. 15…”

Section: Model Simulationmentioning

confidence: 99%

Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model

Guo

Huo

et al. 2020

J Int Med Res

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Objective This prospective study aimed to establish the valproic acid (VPA) population pharmacokinetic model in Chinese patients and realise personalised medication on the basis of population pharmacokinetics. Methods The patients’ clinical information and VPA plasma concentrations were collected from The General Hospital of Taiyuan Iron & Steel (Group) Corporation (TISCO). Nonlinear mixed-effect modelling was used to build the population pharmacokinetic model. To characterise the pharmacokinetic data, a one-compartment pharmacokinetic model with first-order absorption and elimination was used. The first-order conditional estimation with η-ε interaction was applied throughout the model-developing procedure. The absorption rate constant (Ka) was fixed at 2.38 hour−1, and the impact of covariates on clearance and apparent volume of distribution were also explored. Medical records of 60 inpatients were reviewed prospectively and the objective function value (OFV) of the base model and final model were 851.813 and 817.622, respectively. Results Gender was identified as the covariate that had a significant impact on the volume of distribution, and albumin and CYP2C19 genotypes influenced clearance. Conclusion Bootstrap and VPC indicated that a reliable model had been developed that was based on the simulation results, and a simple-to-use dosage regimen table was created to guide clinicians for VPA drug dosing.

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Section: Model Simulationmentioning

confidence: 99%

Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model

Guo

Huo

et al. 2020

J Int Med Res

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“…13e19 However, there are limited sources describing the pediatric PK of ceftazidime to date, although ceftazidime is a commonly used antibiotic for children. Coskun and Atici, 20 Shi et al, 21 Wang et al, 22 and Zwittink et al 23 conducted studies on population PK and dosing optimization of ceftazidime in infected preterm infants and neonates with normal renal function. But there have been no PK studies in pediatric RI patients.…”

Section: Introductionmentioning

confidence: 99%

Dosage Adjustment for Ceftazidime in Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling

Zhou¹,

You²,

et al. 2021

Journal of Pharmaceutical Sciences

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“…[1][2][3] It is not just piperacillin/tazobactam, but many other drugs, where PPK studies have been conducted in neonates and dosing regimens have been recommended, but no clinical validated trials have been conducted to evaluate the effectiveness and tolerance of the drugs. 20,36 Based on the first step, we applied the dose supported by the PPK model to the clinic to observe its effectiveness and tolerance in neonates with EOS. It was a key step to transform clinical data into clinical evidence so as to improve the use of piperacillin/tazobactam in this vulnerable population.…”

Section: Discussionmentioning

confidence: 99%

“…The effectiveness and safety data are limited in neonates, especially in neonates with EOS, which is a very special disease with non‐specific clinical symptoms, absence of specific biomarkers and low positive rate of blood culture 1–3 . It is not just piperacillin/tazobactam, but many other drugs, where PPK studies have been conducted in neonates and dosing regimens have been recommended, but no clinical validated trials have been conducted to evaluate the effectiveness and tolerance of the drugs 20,36 . Based on the first step, we applied the dose supported by the PPK model to the clinic to observe its effectiveness and tolerance in neonates with EOS.…”

Section: Discussionmentioning

confidence: 99%

Clinical utiliy of a model‐based piperacillin dose in neonates with early‐onset sepsis

Hou

Fang

et al. 2021

Brit J Clinical Pharma

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AimsEarly‐onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model‐based dosing regimen of piperacillin/tazobactam in EOS patients.MethodsA prospective, single‐centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg−1, q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected.ResultsA total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14–41.29) weeks. Forty‐seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2–305.8) hours and 31 (30, 5–123) days. There were no obvious adverse events and no infection‐related deaths occurred in the first month of life.ConclusionsA model‐based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.

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Population Pharmacokinetics and Dosing Simulations of Ceftazidime in Chinese Neonates

Cited by 12 publications

References 21 publications

Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model

Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model

Dosage Adjustment for Ceftazidime in Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling

Clinical utiliy of a model‐based piperacillin dose in neonates with early‐onset sepsis

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